Vaccines often include adjuvants to boost immune activity. Examples of known adjuvants include aluminium salts, oil-in-water emulsions, saponins, cytokines, lipids and CpG oligonucleotides. Currently, only aluminium salts and the monophosphoryl lipid MF59™ are approved for human use. However, aluminium salts are subject to safety concerns and are incompatible with some antigens. There is therefore a need to develop further adjuvants.
α-galactosylceramide (α-GalCer) is a glycolipid, more specifically a glycosylceramide, originally isolated from marine sponges [1]. α-GalCer is presented by the MHC class I-like molecule, CD1d, to invariant Natural Killer T cells and was originally investigated for its ability to induce a Natural Killer T cell response against tumour cells [2]. Invariant Natural Killer T cells have been also shown to induce B cell activation, enhancing B cell proliferation and antibody production [3, 4]. Recently, α-GalCer has been shown to act as an adjuvant for a variety of co-administered protein antigens [5]. Coadministration of α-GalCer with irradiated sporozoites or recombinant viruses expressing a malaria antigen has been shown to enhance the level of protective anti-malaria immunity in mice [6]. α-GalCer has also been shown to act as an adjuvant for a DNA vaccine encoding HIV-1 gag and env genes [7].
However, not all vaccines contain protein antigens. Several commercially available vaccines contain saccharide antigens. For example, Pneumovax™ is a vaccine containing saccharide antigens from 23 pneumococcal serotypes. Mencevax™ and Menomune™ are meningococcal vaccines containing saccharide antigens from Neisseria meningitidis A, C, Y and W-135. It would therefore be desirable to extend the use of α-GalCer as an adjuvant to saccharide antigens.
Despite the success of α-GalCer as an adjuvant for DNA and protein antigens, the inventors have surprisingly found that it does not act as an adjuvant for some saccharide antigens. On the contrary, administration of α-GalCer with these antigens has been found to result in a substantial decrease in antibody titres relative to unadjuvanted controls. It is an object of the invention to overcome the problem of inhibition of anti-saccharide antibody responses when α-GalCer is present.